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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vulnerability to arrhythmias can be influenced by two conditions: a dynamic (beat-to-beat) variation of repolarization sequence, and a state of heterogeneity of repolarization, i.e. a greater than normal dispersion of recovery time. The first condition is well reflected by T-wave alternans, a phenomenon characterized by alternation on every other beat basis of amplitude and morphology of T waves. Experimental studies provided evidences of close temporal correlations between ischemia-induced alternans, dispersion of repolarization and susceptibility to ventricular fibrillation. Gross T-wave alternans can be occasionally observed in patients with long QT syndrome or during acute ischemia before the onset of arrhythmias. Recent studies have demonstrated that measurement of microvolt level T-wave alternans at rest and during exercise is a promising technique for the identification of patients at risk of ventricular arrhythmias and sudden death. A state of repolarization inhomogeneity can be revealed by methods which analyze a single cardiac beat. The QT dispersion, defined as the difference between maximum and minimum QT interval measured at 12 lead ECG, is the most simple and widely used index of repolarization inhomogeneity. The major limitation is that this measure cannot be related to the actual spatial heterogeneity of repolarization, since each surface lead reflects, in different degree, the electrical activity of the whole heart. The majority of studies reported that, in various pathological conditions, the QT dispersion is higher in patients with than without ventricular arrhythmias. On the other hand, a recent large prospective study in post-myocardial infarction patients failed to demonstrate the predictive value of QT dispersion, even when measured with the best available methodology. Body surface potential mapping has proven to be a useful method for detecting repolarization inhomogeneities not revealed by the analysis of conventional ECG leads. Different methods of analysis of the potential maps have been used. By applying principal component analysis of the ST-T waves, we computed the similarity index, defined as the ratio of the first principal component to the sum of all remaining components. A low value of similarity index suggests a high degree of repolarization inhomogeneity. The similarity index was found significantly lower in patients with idiopathic long QT syndrome and in patients with arrhythmogenic right ventricular dysplasia with episodes of ventricular tachycardia than in normal subjects. Future researches should aim at identifying novel reliable indices of repolarization inhomogeneity, first deduced from extensive body surface mapping, then possibly computed from digital recording of the 12 conventional leads.
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PMID:[Heterogeneities of ventricular repolarization and vulnerability to arrhythmia. How to detect them with noninvasive methods?]. 1037 87

Recent studies have shown that ventricular myocardium is composed of at least 3 electrophysiologically distinct cell types: epicardial, endocardial, and M cells. Action potentials recorded from epicardial and M cells, unlike those recorded from endocardium, display a spike-and-dome morphology, the result of a prominent transient outward current-mediated phase 1. M cells are distinguished from endocardial and epicardial cells by the ability of their action potential to prolong disproportionately in response to a slowing of rate and/or to agents with class III actions. This intrinsic electrical heterogeneity contributes to the inscription of the electrocardiogram as well as to the development of a variety of cardiac arrhythmias. The transmural dispersion of repolarization is in large part responsible for the inscription of the J wave and T wave of the electrocardiogram. Because full repolarization of epicardium defines the peak of the T wave and that of the M cells, the end of the T wave, the interval between the peak and the end of the T wave provides a valuable index of transmural dispersion of repolarization. Differences in the response of the 3 cell types to pharmacologic agents and/or pathophysiological states often results in amplification of intrinsic electrical heterogeneities, thus providing a substrate as well as a trigger for the development of reentrant arrhythmias, including torsade de pointes (TdP) commonly associated with the long QT syndrome (LQTS) and the polymorphic ventricular tachycardia/fibrillation encountered in patients with the Brugada syndrome. Early repolarization of the epicardial action potential results in abnormal abbreviation of action potential duration due to an all-or-none repolarization at the end of phase 1 of the epicardial action potential. The loss of the action potential dome in epicardium but not endocardium gives rise to a large dispersion of repolarization across the ventricular wall, resulting in a transmural voltage gradient that manifests in the electrocardiogram as an ST segment elevation (or idiopathic J wave). Under these conditions, heterogeneous repolarization of the epicardial action potential gives rise to phase 2 reentry, which provides an extrasystole capable of precipitating ventricular tachycardia/fibrillation (or rapid TdP). Experimental models displaying these phenomena show electrocardiographic characteristics similar to those of the Brugada syndrome as well as those encountered during acute ischemia. Transmural dispersion of repolarization is also greatly amplified in LQTS. Disproportionate prolongation of the M-cell action potential contributes to the development of long QT intervals, wide-based or notched T waves, and a large transmural dispersion of repolarization, which provides the substrate for the development of a polymorphic ventricular tachycardia closely resembling torsade de pointes. An early afterdepolarization-induced triggered beat is thought to provide the extrasystole that precipitates TdP. Pharmacologic models of the LQT1, LQT2 and LQT3 forms of LQTS mimic the distinctive electrocardiographic, electrophysiologic, and pharmacologic responses observed in patients with these 3 different genetic syndromes. In LQTS, as in the Brugada syndrome, a mutation in an ion channel gene (in some cases the same gene--SCN5A) is responsible for the development of a large transmural dispersion of repolarization, which serves to provide the arrhythmogenic substrate tha can lead to sudden death.
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PMID:Transmural dispersion of repolarization and arrhythmogenicity: the Brugada syndrome versus the long QT syndrome. 1068 20

Class IA, IC, and III antiarrhythmic drugs prolong ventricular repolarization (VR) which is manifest as QT interval prolongation on the surface electrocardiogram. These drugs may prolong VR in a spatially heterogeneous manner which results in increased dispersion of VR. This may be manifest as increased QT interval dispersion. Antiarrhythmic drug-induced decreases in QT interval dispersion are associated with antiarrhythmic efficacy in patients with the long QT syndrome and in patients with sustained ventricular tachycardia. Antiarrhythmic drug-induced increases in QT interval dispersion are associated with ventricular proarrhythmia secondary to torsades de points ventricular tachycardia. A number of factors may modulate the effects of antiarrhythmic drugs on dispersion of VR, including the disease state, transient ischemia, electrolyte abnormalities, changes in autonomic tone, and hemodynamic stress.
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PMID:Effects of antiarrhythmic drugs on QT interval dispersion--relationship to antiarrhythmic action and proarrhythmia. 1076 15

Cardiac sodium (Na) channels are dynamic molecules that undergo rapid structural changes in response to the changing electrical field in the myocardium. Inherited mutations in SCN5A, the gene encoding the cardiac Na channel, provoke life-threatening cardiac arrhythmias, often by modifying these voltage-dependent conformational changes. These disorders (i.e. the long QT syndrome and Brugada syndrome) may serve as valuable models for understanding the mechanistic linkages between Na channel dysfunction and cardiac arrhythmias in more common, acquired conditions such as cardiac ischemia. In addition, the balance between therapeutic and adverse effects from Na channel blockade by antiarrhythmic compounds may be shifted by subtle alterations in Na channel function. This review examines recent studies that tie key loci in the Na channel primary sequence to its dynamic function, while examining the emerging themes linking Na channel structure, function, and pharmacology to inherited and acquired disorders of cardiac excitability.
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PMID:The cardiac sodium channel: gating function and molecular pharmacology. 1127 15

Electrical alternans represents a variation in the morphology of electrocardiographic complexes on an every-other-beat basis in an ABABAB... pattern. Apparent electrical alternans associated with pericardial effusion results from rotation of the heart in the pericardial sac, and not true alternation in electrical conduction patterns. In contrast, true electrical alternans results from an alternation in electrical conduction patterns in the heart itself. Repolarization alternans is true electrical alternans associated with the ST segment and T wave of the electrocardiogram (ECG). Here we will focus on T-wave alternans (TWA) and its association with susceptibility to ventricular tachyarrhythmias. Electrical alternans was reported in the literature as early as 1909. Historically, electrical alternans has been regarded as a fairly rare electrocardiographic abnormality. Case reports of electrical alternans have been associated with a variety of disease states, including acute ischemia, Prinzmetal's angina, a variety of electrolyte abnormalities, and the long QT syndrome. Interestingly, patients born with the prolonged QT syndrome have a very high incidence of sudden cardiac death at an early age. Schwartz and Malliani showed that patients with the prolonged QT syndrome who do not demonstrate alternans at rest, may evidence alternans during stress such as emotional excitement. Thus, over the years electrical alternans has been associated anecdotally with conditions associated with an increased risk of ventricular arrhythmias. In 1948, Kalter reviewed the world literature on electrical alternans and found a total of 41 reported cases. In addition, he reviewed clinical ectrocardiograms from 6059 patients and found five new cases (incidence of less than 1 in 1000 patients). Interestingly, he found a very high mortality, 62%, associated with this condition. Despite the clinical associations reported in the literature, the consensus view of electrical alternans until recent years has been that alternans is an electrocardiographic curiosity rarely encountered in clinical practice which, when identified, does not have specific clinical significance.
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PMID:Clinical utility of T-wave alternans. 1154 10

QT dispersion reflects in homogenecity of ventricular repolarization. It is calculated using 12-leads standard synchronized ECG or 24-hours Holter monitoring. The most common used indicators are: QT dispersion (QTd), based on Bazett's formula corrected for heart rate QT dispersion (QTcd) and QT dispersion ratio (QTdR). QT apex and QTd corrected for total number of leads ECG in which QT interval was counted are rare used. Increased QT dispersion is observed among others: following myocardial infarction (MI), coronary heart disease (CAD), hypertension, chronic heart failure (CHF), long QT syndrome, as well as diabetes. Following mentioned diseases increased QT dispersion has prognostic value for sustained ventricular tachycardia. Dispersion of repolarization > or = 80 ms after MI is a risk factor for sudden cardiac death. Following acute MI decrease of QT dispersion after successful thrombolytic therapy is observed and its value > or = 100 ms is regarded as a marker of reperfusion insufficiency. QT dispersion in patients with CAD correlates with extent of ischemia and decreases after coronary angioplasty (PTCA). In recent years beneficial effect of angiotensin-converting enzyme inhibitors and beta-adrenolytic therapy on QT dispersion was described. Actually the improvement of computerised methods in assessment of QT dispersion is observed, but it require further investigations.
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PMID:[Measurement dispersion of the QT interval and its significance in different diseases]. 1157 33

Recent studies have established the presence of three distinct cell types in the ventricular myocardium: epicardial, M and endocardial cells. Epicardial and M cell action potentials differ from endocardial cells with respect to the morphology of phase 1. These cells possess a prominent transient outward current (I(to))-mediated notch responsible for the 'spike and dome' morphology of the epicardial and M cell response. M cells are distinguished from the other cell types in that they display a smaller slowly activating delayed rectifier current (I(Ks)), but a larger late sodium current (late I(Na)) and sodium-calcium exchange current (I(Na-Ca)). These ionic distinctions underlie the longer action potential duration (APD) and steeper APD-rate relationship of the M cell, which is more pronounced in the presence of antiarrhythmic agents with class III actions. The preferential prolongation of the M cell action potential results in the development of a transmural dispersion of repolarization (TDR), which can be estimated from the electrocardiogram (ECG) as the interval between the peak and the end of the T wave (QTpeak-QTend interval). Using the canine arterially perfused ventricular wedge model, transmembrane action potentials of the various cardiac cell types can be correlated to the waveforms of the ECG, providing insight into the cellular etiology of ECG abnormalities. Two congenital syndromes of sudden cardiac death that have been modeled using this technique are the long QT and Brugada syndromes. The long QT syndrome has been linked to 5 gene mutations on chromosomes 3, 7, 11, and 21. Mutations in the cardiac sodium channel SCN5A have been linked to families with a history of the Brugada syndrome. Although the etiologies of these two syndromes are different, lethal arrhythmias in both are thought to arise due to amplification of intrinsic electrical heterogeneities. Similar mechanisms are likely responsible for life-threatening arrhythmias in a variety of other cardiomyopathies ranging from heart failure and hypertrophy, which involve mechanisms similar to those operative in LQTS, to ischemia and infarction, which may involve mechanisms more closely resembling those responsible for the Brugada syndrome.
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PMID:Electrical heterogeneity within the ventricular wall. 1177 69

The sequencing of human genome was completed in 2001. The position of particular DNA base is established-i.e. we know all "letters" in the "book" but we understand only limited number of "words" i. e. only limited number of genes was identified. And the human genome consists of about 30,000 genes from which through the mechanism of alternative RNA splicing more than 100,000 genes can be derived. All the genes of one individual form the genotype. The expression of genotype in particular environment forms the phenotype. What is not present in genotype can neither be present in phenotype. In the last decade a substantial progress was achieved in understanding of membrane processes mostly due to research of relatively rare inherited monogenous arrhythmic syndromes--first of all the long QT syndrome. It is caused by mutations in ion channel genes and it provides a model of arrhythmogenesis on molecular level. Ventricular arrhythmias are important cause of mortality in patients with cardiovascular diseases. New studies have provided strong evidence for familial sudden cardiac death (SCD) aggregation and therefore also genetic influence. Parental history of SCD increases the relative risk of SCD for offspring to 1.8. In the case of both maternal and paternal SCD events the risk for offspring is a remarkable 9.4. There are 3 pathways by which genetic variation may contribute to risk for SCD: 1. alterations in electrogenesis and conduction, 2. formation and stability of atherosclerotic plaque, thrombogenesis and ischemia within the coronary circulation, 3. control of myocardial excitability and vascular motorics. The main objective of both today and future research is identification of inheritable "molecular" risk factors of arrhythmias. Understanding of this level of pathophysiological processes will subsequently lead to new generation of both diagnostic and therapeutic methods.
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PMID:[Molecular genetic aspects of arrhythmias]. 1458 30

Although long QT syndrome (LQTS) and coronary occlusion-reperfusion (O/R) are arrhythmogenic, they affect ventricular action potential duration (APD) differently. In contrast to the prolonged APD in LQTS, ischemia abbreviates APD after a transient prolongation. Thus we hypothesized that the dynamic interactive effects of ischemia and LQTS on APD and its dispersion would affect ventricular arrhythmogenicity. We mapped transmural distribution of action potentials in 6 groups of 10 isolated wedges of canine ventricular walls: LQTS-O/R, LQTS only, and O/R only, with separate groups for pacing cycle lengths (PCL) of 1,000 and 2,000 ms. We created type 3 LQTS with anemone toxin (ATX) II followed >30 min later by arterial occlusion (40 min) and reperfusion (>100 min). Arterial occlusion initially (first 4 min) prolonged and then shortened APD. Early afterdepolarizations (EADs) occurred during the initial 4 min of occlusion in 4 of the 10 LQTS-O/R wedges at PCL of 2,000 ms but not in the other groups. Reperfusion restored APD in the O/R-only groups but caused APD to overshoot its original duration, indicating depressed repolarization reserve, in the LQTS-O/R group. Reperfusion increased the dispersion of APDs and initiated ventricular tachycardia-fibrillation in 7 of 10 and 6 of 10 LQTS-O/R wedges and in 2 of 10 and 1 of 10 O/R-only wedges at PCLs of 1,000 and 2,000 ms, respectively. The LQTS-only wedges exhibited neither EADs nor ventricular tachycardia. We conclude that coronary O/R increased the arrhythmogenicity of LQTS via cumulative prolongation of APD, increase in repolarization dispersion, and suppression of repolarization reserve.
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PMID:Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome. 1617 58

We report 2 patients in whom transient marked QT prolongation occurred after successful emergent percutaneous coronary intervention (PCI) for acute coronary syndrome. One patient developed torsades de pointes. In both cases, the QT interval became markedly prolonged within 24 hours after PCI, and this prolongation persisted for 4 days. The T waves had a giant and bizarre negative shape with a prolonged T-wave peak to T-wave end interval. No new-onset ischemia or congenital long QT syndrome was related to the episodes. The patients had not taken any drugs that could have prolonged the QT interval, and their serum potassium levels were within normal limits. Torsades de pointes following successful PCI for acute coronary syndrome is uncommon, but acquired long QT syndrome should be considered and treated in patients in whom giant and bizarre negative T waves and QT prolongation develop after PCI.
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PMID:Torsades de pointes related to transient marked QT prolongation following successful emergent percutaneous coronary intervention for acute coronary syndrome. 1832 36


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